Biomedical subjects
Shunji Mishiro
Publications and source records attributed to Shunji Mishiro.
Severe hepatitis E virus infection after ingestion of uncooked liver from a wild boar.
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Zoonotic transmission of hepatitis E virus from deer to human beings.
Zoonosis has been suggested for hepatitis E virus (HEV) infection, but so far is based only on indirect evidence. We experienced a series of cases of HEV infection among people who had eaten uncooked deer meat 6-7 weeks before. On testing, a left over portion of the deer meat, kept frozen to eat in the future, was positive for HEV RNA, whose nucleotide sequence was identical to those from the patients. Patients' family members who ate none or very little of the deer meat remained uninfected. These findings provide direct evidence for HEV infection to be a zoonosis.
The dinucleotide microsatellite polymorphism of the IFNAR1 gene promoter correlates with responsiveness of hepatitis C patients to interferon.
We studied a possible correlation between the dinucleotide microsatellite polymorphism of the interferon alpha/beta receptor-1 gene (IFNAR1) and responsiveness of hepatitis C patients to interferon therapy. The length of GT-repeat (n of (GT)(n)) in the IFNAR1 promoter was determined in 157 patients, of whom 50 were responders and 107 were nonresponders to interferon. The genotypes 5/5 (i.e. homozygotes of (GT)(5)) and 5/14 (i.e. heterozygotes of (GT)(5) and (GT)(14)) were more frequently found in responders than in nonresponders: 80 versus 58%, P=0.008. Thus, determining (GT)(n) of the IFNAR1 promoter may help predict treatment outcome in patients treated with interferon alpha and/or beta. In addition, we sought for genetic polymorphism in the promoter region of the interferon alpha/beta receptor-2 gene (IFNAR2), and found single nucleotide polymorphisms (SNPs) at -134 and -75. But these SNPs did not show a clinical significance, as compared with the GT-repeat in IFNAR1, in the context of interferon responsiveness.
A case report: two patients with fulminant hepatitis E in Hokkaido, Japan.
Hepatitis E virus (HEV) has been listed as one of the major agents that cause fulminant hepatitis in HEV-endemic areas, but not in non-endemic areas. Recently, however, we experienced two cases of fulminant hepatitis E in Hokkaido, Japan: case-1 was a 34-year-old woman and case-2, a 51-year-old man, neither having a history of travelling outside Japan or contact with travellers abroad or foreigners. HEV RNA was detected in their acute-phase serum and sequencing analyses indicated that they were infected with different strains of HEV: genotype III in case-1 and IV in case-2. Case-1 patient deceased after liver transplantation, while case-2 patient survived. Based on these cases, we suggest that HEV should be considered as an aetiologic agent for fulminant hepatitis, even in non-endemic areas.
A genotype IV hepatitis E virus strain that may be indigenous to Changchun, China.
We sequenced the RNA genome of hepatitis E virus (HEV) recovered from an acute hepatitis patient living in Changchun, China. The HEV-CCC220 isolate thus obtained was 7,193 nt in length and contained ORF1 (5121 nt, 1706 aa), ORF2 (2025 nt, 674 aa), and ORF3 (345 nt, 114 aa) plus uncompleted 5' and 3' untranslated regions. When compared with full-genome isolates so far reported, the CCC220 isolate segregated to genotype IV although the nucleotide similarity to the previous genotype IV isolates was only 83.9-85.6%. Comparison of a partial sequence (300 nt) within the ORF2 between the genotype IV isolates from China, Taiwan and Japan also indicated the phylogenetic uniqueness of the CCC220 isolate: even the highest homology was less than 90%. These findings suggest that the CCC220 isolate might represent HEV strains that are indigenous to Changchun, China.
Full-length sequences of six hepatitis E virus isolates of genotypes III and IV from patients with sporadic acute or fulminant hepatitis in Japan.
OBJECTIVE: Ranges of variation and conservation in sequence need to be defined for detecting and genotyping hepatitis E virus (HEV). METHODS: Six HEV isolates from Japanese patients were sequenced over the entire genome and compared phylogenetically along with 16 reported HEV isolates, including two from pigs. RESULTS: Three of the six HEV isolates were of genotype III, and the remaining three were of genotype IV. Local clusterings of Japanese HEV isolates were observed in the phylogenetic analyses, including a swine HEV isolate reported previously (swJ570). All six HEV isolates possessed three open reading frames (ORFs). The ORF3 in the three isolates of genotype III were in a different reading frame, while that in the three isolates of genotype IV were in the same reading frame as ORF1. A stretch of 46-96 nucleotides was identified, point mutations and deletions in which were specific for the four genotypes (I-IV). A polymerase chain reaction method was developed with 9 nested universal primers, deduced from conserved regions in the 5'-terminal sequences of the 22 HEV genomes. CONCLUSIONS: Conserved and genotype-specific variation in HEV sequences, identified in the comparison of 22 full-length genomes, would be useful in designing primers for sensitive detection and specific genotyping of HEV RNA.
Genetic heterogeneity of hepatitis E virus recovered from Japanese patients with acute sporadic hepatitis.
The recent discovery of a presumably Japan-indigenous hepatitis E virus (HEV) strain (JRA1) spurred analysis of additional isolates from 7 cases of acute sporadic hepatitis E infection. Comparison of a 326-nucleotide region from open-reading frame 1 indicated that 1, 3, and 3 isolates segregated to genotypes I, III, and IV, respectively. Six patients had not traveled abroad recently. One patient had traveled to Hawaii 1 month before becoming ill, and the nucleotide sequence of the HEV isolate infecting her resembled those of US isolates (89%-91% nucleotide identity). However, the isolate was even more homologous to 2 other Japanese isolates (95%-97% nucleotide identity), suggesting that it is more likely a domestic, rather than an imported, strain. Three genotype IV isolates from Japan also had a higher homology to each other (100% amino acid identity) than to 2 Chinese isolates (97%-98% amino acid identity). These findings suggest that HEV strains of at least 3 different genotypes have already made inroads and are spreading in Japan.
Demographic, clinical, and virological characteristics of hepatocellular carcinoma in Asia: survey of 414 patients from four countries.
Demographic, etiological, clinical characteristics and treatment of hepatocellular carcinoma (HCC) were surveyed in 414 patients in Asia, including 107 from China, 15 from India, 101 from Indonesia and 191 from Japan. Males predominated in all countries, accounting for up to 75%. The mean +/- SD age at the development of HCC was about 10 years older for the patients from Japan (63.8 +/- 9.5, P < 0.001) and India (63.1 +/- 11.2, P < 0.05) than those from China (54.0 +/- 13.7) and Indonesia (53.7 +/- 14.2). Hepatitis B surface antigen (HBsAg) in serum was detected in 67% of patients from China who were tested, 27% from India, 21% from Indonesia and 18% from Japan, whereas antibody to hepatitis C virus was detected in 4%, 53%, 40% and 70%, respectively; co-occurrence of hepatitis B and C infections was seen only in 7%, 0%, 2%, and 1%, leaving an etiology other than hepatitis viruses in 22%, 20%, 36% and 11%. HCC was diagnosed primarily by ultrasonography in China (43%) and Japan (52%), and on physical examination in India (60%) and Indonesia (52%). The size of the largest tumor exceeded 5.0 cm in diameter only in 24% of the patients from Japan, much less often than in 67%, 87%, and 71%, respectively, of those from China, India and Indonesia (P < 0.001). The most favored treatment was chemolipidolization in China (81%) and Japan (81%), whereas it was transarterial embolization in India (13%) and Indonesia (26%). These results highlight common as well as distinct characteristics of HCC in Asia, and warrant the need for close cooperation toward early diagnosis and effective treatment of HCC.
Clinical outcomes of hepatitis B virus (HBV) genotypes B and C in Japanese patients with chronic HBV infection.
The aims of this retrospective survey were to determine the epidemiologic distribution of hepatitis B virus (HBV) genotypes and analyze the genotype-related clinical differences among Japanese patients with chronic HBV infection. The 158 surveyed patients with chronic HBV infection lived in Fukuoka and Okinawa were serially tested for serum alanine aminotransferase (ALT) and hepatitis B e antigen (HBeAg). Follow-up was for a period of 10.8 +/- 6.4 years (mean +/- SD). The HBV genotypes were determined in sera by an enzyme-linked immunosorbent assay and detection of HBV DNA in serum was done by the transcription-mediated amplification-hybridization protection assay. Genotypes B and C were found in 58 (36.7%) and 100 (63.3%) of the patients, respectively. Genotype B was predominant in Okinawa (B = 86.9%, C = 13.1%), whereas genotype C was predominant in Fukuoka (B = 5.2%, C = 94.8%). The HBeAg positivity and ALT abnormality rates at the start of the observation period were significantly higher in patients with genotype C (66.0% and 84.0%) than in patients with genotype B (34.5% and 22.4%) (P < 0.05, respectively). The annual rate of spontaneous HBeAg disappearance in patients with genotype B was much higher than in patients with genotype C (8.38% versus 2.34%, respectively). Patients with genotype C who were continuously HBeAg negative from entry had a significantly higher ALT abnormality (58.8%) than those with genotype B (19.2%) (P < 0.05). Interestingly, patients with genotype C who became HBeAg negative after treatment with interferon had a high ALT abnormality (58.8%). All patients with an ALT abnormality were positive for HBV DNA in their serum. These findings indicate that patients with HBV genotype C have more severe liver deterioration because of the delay of HBeAg disappearance and continued HBV replication after HBeAg disappearance.